{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:57:26Z","timestamp":1791388646777,"version":"4.3.3"},"reference-count":49,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82200942"],"award-info":[{"award-number":["82200942"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100022944","name":"Suzhou Gusu Medical Youth Talent","doi-asserted-by":"publisher","award":["GSWS2023038"],"award-info":[{"award-number":["GSWS2023038"]}],"id":[{"id":"10.13039\/100022944","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100022944","name":"Suzhou Gusu Medical Youth Talent","doi-asserted-by":"publisher","award":["GSWS2023050"],"award-info":[{"award-number":["GSWS2023050"]}],"id":[{"id":"10.13039\/100022944","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018556","name":"Science and Technology Program of Suzhou","doi-asserted-by":"publisher","award":["SKY2023006"],"award-info":[{"award-number":["SKY2023006"]}],"id":[{"id":"10.13039\/501100018556","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diabetic cardiomyopathy (DbCM) is driven by metabolic inflexibility and impaired mitochondrial clearance. While the pro\u2010resolving lipid mediator Maresin 1 (MaR1) shows therapeutic promise, its capacity to correct the underlying metabolic\u2010epigenetic disturbances in DbCM remains undefined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials<\/jats:title>\n                    <jats:p>Db\/db mice and palmitic acid (PA)\u2010exposed H9c2 cardiomyocytes were treated with MaR1. Cardiac function and structure were assessed by echocardiography and histological analysis. Myocardial oxidative stress, inflammation, and key molecular pathways were evaluated via immunoblotting, qPCR, immunohistochemistry, and transmission electron microscopy. The role of the putative receptor LGR6 was investigated using siRNA\u2010mediated knockdown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MaR1 improved cardiac diastolic function, attenuated pathological hypertrophy and interstitial fibrosis, and reduced oxidative stress and inflammatory markers in db\/db mice. Mechanistically, MaR1 activated AMPK signaling, restoring the expression of crucial enzymes for both fatty acid oxidation (CPT1B) and glycolysis (PFK\u20101, HK2). This metabolic reprogramming elevated intracellular lactate, which in turn replenished the deficient global protein lysine lactylation (Kla). Concurrently, MaR1 reactivated the PINK1\/Parkin pathway, restoring mitophagy\u2010associated signaling. In vitro, exogenous lactate supplementation recapitulated these effects. Importantly, LGR6 silencing abrogated all MaR1\u2010induced benefits, including glycolytic activation, lactylation rescue, and mitophagic recovery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MaR1 protects against DbCM by signaling through LGR6 to restore metabolic flexibility, thereby fueling a lactate\u2010dependent lactylation program that is critically associated with the reactivation of mitochondrial quality control via mitophagy. This study unveils a critical metabolic\u2010epigenetic axis as a novel therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jdi.70464","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:39:44Z","timestamp":1791387584000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>LGR6<\/scp>\n                    couples maresin 1 signaling to glycolytic flux and protein lactylation for the rescue of diabetic cardiomyopathy"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6262-866X","authenticated-orcid":false,"given":"Bin","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Endocrinology First Affiliated Hospital of Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu College of Nanjing Medical University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu College of Nanjing Medical University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqiong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu College of Nanjing Medical University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Cardiology The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu College of Nanjing Medical University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiran","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Cardiology The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu College of Nanjing Medical University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Cardiology The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu College of Nanjing Medical University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bimin","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology First Affiliated Hospital of Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nannan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology The Affiliated Suzhou 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